The invention relates to a method for the analysis of a component of a medical sample by means of an autoanalyzer, in which a reaction of the sample with a reagent system is carried out and a physically measurable quantity X resulting from the reaction of the sample with a reagent system is measured. At least one measured value R is determined here for a specified sample. This is converted into an analytical result A in a processing unit of the analyzer.
Many different methods can be used in medical laboratory analysis for determination of the desired analysis result A, where fully automatic analyzers are mostly used for carrying out the method. The samples are, as a rule, body fluids, especially blood and urine, and are investigated in order to obtain an analytical result A concerning one of the components contained in them.
The result A is usually (in quantitative analyses) the concentration C of the component. In qualitative analyses it is the assignment of the sample (with regard to the investigated analyte) to a medico-analytical state, for example, the statement that the analysis result is positive or negative. More than two states, for example, `high`, `normal`, and `low`, are sometimes also usual here. However, other medically significant results of an analysis of a medical sample are also to be regarded as an analytical result A as defined by the invention, for example, a statement on the presence of a disease made directly (that is, without any concentration value or any medico-analytical condition being indicated) from the analysis. This is at present still rather unusual, though the invention is creating new possibilities in this direction.
Expressed in terms of measurement electronics, the analytical result A is an analogous or logical state which is normally determined from at least one measured value R fully automatically and embodies an item of medically relevant information.
The analysis is always based on the reaction of the sample with one or more reagents (which are together known as the reagent system) suitable for the analysis of a specified component (usually known as the `analyte` or `parameter`) of the sample. The reagents are mixed in the autoanalyzer with the sample, either all at once or at predetermined intervals. The details of the method of analysis, apart from specially discussed peculiarities in certain practical forms of the invention, are not of importance for the present invention.
Examples of common physically measurable quantities X include the determination of a color change by means of photometry; nephelometry and turbidimetry for measuring the turbidity of a sample; sensitive light detection by means of photomultipliers, when X is a fluorescence signal; or current- or voltage-measurement for the case where the quantity X is of an electrical nature in electrochemical tests. The physically measurable quantity X is generally measured with a suitable method and technically converted into an electrical measurement signal. The measured value of the measurement signal is the value R, which is a definite measure of the quantity X.
Autoanalyzers generally fully automatically determine an analytical result A, which is usually a concentration C, from at least one measured value R. Several measured values R.sub.i are frequently determined on one sample, where a derivative variable is calculated in the processing unit from at least two measured values and can be termed the measurement result. In simple cases, the measured value R, or the measurement result deduced from at least two measured values R.sub.i, can be clearly and accurately linked with the concentration C by a simple functional relationship, usually known as the calibration curve. The measured value and the measurement result form here the calibration input variable of the calibration Y=f(C).
In the evaluation it must always be taken into account that the analysis reactions are time-dependent. The situation is relatively simple when the reaction or series of reactions resulting in the measurable physical quantity X proceed very rapidly. In this case, the measured value R is determined at a point in time when the analysis reaction is essentially completed and is immediately used as the input calibration variable Y. This is known as an end-point determination.
Another relatively simple example is the case where a relatively slow reaction is decisive for the alteration of the quantity X with time and from which there results over a certain length of time a time-related alteration (`kinetic`) of the measured value R which follows a linear or other simple functional relationship. X is repeatedly measured here at various measuring times t.sub.i within the above-mentioned period. A measurement result describing the kinetic (for example, the alteration dR/dt(t.sub.i) of the measured value R per time unit at a certain time) is calculated from the measured value R.sub.i (t.sub.i) and serves as the input variable Y for the determination of the analytical result A.
The alteration of X with time often depends in a very complex manner on the kinetic behavior of a number of partial reactions, which play a role in the overall reaction of the analysis system with the sample. This results in a complex course of the time-related alteration of the quantity X, which is known as complex reaction kinetics. The invention is particularly directed at such cases of complex reaction kinetics.
Various known approaches exist for the evaluation of the complex reaction kinetics resulting from several overlapping chemical kinetics of the individual reactions. For example, an attempt can be made to describe the complex reaction kinetics in the form of separate differential equations for the partial reactions, where the function parameters of the differential equations correspond to measurable reaction kinetic values. The complexity of the actual reaction system, however, necessitates idealizing model hypotheses that restrict the validity range of the model results. For this reason, phenomenological models, in which the function parameters bear no direct relationship to the individual reactions, but are frequently interpreted as a measure of a specific determined property of the reaction under consideration, have been proposed. Finally, there exist purely statistical models for describing the reaction kinetics. Each of the approaches has certain advantages, though development of the model is very demanding in terms of cost, labor and time. The capacity of a model to adapt to altered conditions (for example, a change of the reagent composition or, in certain circumstances, just of the reagent batch) is nevertheless small, and the accuracy and reliability of the evaluation of the measurement results, and of the determination of the analytical results from this, leaves much to be desired.
The processing unit of the autoanalyzer, in addition to determining the concentration and/or a medico-analytical state from the measured values, usually fulfills a number of other functions that contribute to the determination of a correct analytical result A. These usually include the plausibility testing of the measured values, identification of the reagent production batch, recognition of other reagent and apparatus conditions, detection of errors, and, in some cases, the correlation of differing measurement data obtained on one and the same sample or of measurement data on several samples. The invention also relates to such supplementary functions of the processing unit.